MDAI

Pharmacodynamics

MDAI acts as a selective and well-balanced serotonin and norepinephrine releasing agent (SNRA) with much less (~10-fold lower) effect on dopamine release.^[2] In addition to inducing the release of the monoamine neurotransmitters, MDAI also inhibits their reuptake.^[10] For comparison to MDAI, MDA and MDMA are well-balanced releasing agents of serotonin, norepinephrine, and dopamine (SNDRAs).^[2] Conversely, the profile of monoamine release with MDAI is very similar to that of (R)-MDMA (levo-MDMA), which like MDAI is also a well-balanced SNRA with about 10-fold reduced impact on dopamine release, though MDAI is several-fold more potent than (R)-MDMA in vitro.^[14][2]

In contrast to MDMA, MDAI shows no affinity for any of the serotonin receptors (K_i = all >10 μM).^[2] This notably includes the serotonin 5-HT_2A receptor, which is implicated in producing psychedelic effects, and the serotonin 5-HT_2B receptor, which is implicated in causing cardiac valvulopathy.^[2][15] However, MDAI shows significant affinity for all three of the α₂-adrenergic receptors (K_i = 322 to 1121 nM).^[2]

The family of drugs typified by MDMA produce their effects through multiple mechanisms of action in the body, and consequently produce three distinct cues which animals can be trained to respond to: a stimulant cue typified by drugs such as methamphetamine, a psychedelic cue typified by drugs such as LSD and DOM, and an "entactogen-like" cue which is produced by drugs such as MDAI and MBDB. These drugs cause drug-appropriate responses in animals trained to recognize the effects of MDMA, but do not produce responses in animals trained selectively to respond to stimulants or hallucinogens. Because these compounds selectively release serotonin in the brain but have little effect on dopamine or noradrenaline levels, they can produce empathogenic effects but without any stimulant action, instead being somewhat sedating.^{[22][23][24][25][26][27][28]}

MDAI shows substantially lower serotonergic neurotoxicity than MDMA in animals and has been described as a "non-neurotoxic" analogue of MDMA.^[7][8][9] However, MDAI still shows weak serotonergic neurotoxicity both alone and particularly in combination with amphetamine in animals.^[7][8][9] As such, MDAI does not appear to be a fully non-neurotoxic alternative to MDMA.^[7][8][9]

Pharmacokinetics

The duration of MDAI in humans appears to be similar to that of MDMA at 2 to 5 hours^[4] or up to around 6 hours.^[1]

Synthesis

MDAI can be produced from 3-(3,4-methylenedioxyphenyl)propionic acid^[29] which is converted to the acid chloride and then heated to produce 5,6-methylenedioxy-1-indanone. Treatment of the indanone with amyl nitrite in methanol with HCl afforded the hydroxyimino ketone. This is reduced to the 2-aminoindan following a modification of Nichols' earlier method from a paper discussing DOM analogues,^[30] using a Pd/C catalyst in glacial acetic acid with catalytic H₂SO₄.

Analogues

Analogues of MDAI include 2-aminoindane (2-AI), NM-2-AI, MDMAI, MEAI (5-MeO-2-AI), MMAI, and 5-IAI, among others.

Recreational use

MDAI has been advertised as a designer drug. It started to be sold online from around 2007, but reached peak popularity between about 2010 to 2012, after bans on mephedrone came into effect in various countries. Many internet-sourced products claimed to be MDAI have been shown to contain mephedrone or other cathinones, while generally containing no MDAI. The number of internet searches for MDAI has been considerably higher in the United Kingdom compared to Germany and the United States.^[11]

Legal status